Reduced Risk of Intraocular Bleeding with Novel Oral Anticoagulants

The main outcomes and measures were intraocular bleeding events and associated risk ratio for NOACs, compared with warfarin.

Novel oral anticoagulants (NOACs) lead to a one-fifth reduction in the risk of intraocular bleeding, compared with warfarin in patients with atrial fibrillation (AF) or venous thromboembolism (VT), according to a new Australian study.

Sun et al. conducted a systematic review and meta-analysis of 12 Phase III randomized clinical trials (N=102,627 patients) that enrolled patients with AF or VT, compared a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) with warfarin, and recorded event data on intraocular bleeding. The main outcomes and measures were intraocular bleeding events and associated risk ratio for NOACs, compared with warfarin.

The researchers found that randomization to novel oral anticoagulants was associated with a 22% relative reduction in intraocular bleeding, compared with warfarin (risk ratio, 0.78; 95% CI, 0.61–0.99). Moreover, no significant heterogeneity was observed (I2 = 4.8%, P=0.40) between the trials.

Subgroup analyses showed comparably lower risks of intraocular bleeding with NOACs, with no significant difference based on the indication for anticoagulation (P for heterogeneity = 0.49) or the NOAC type (P for heterogeneity = 0.15). 

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Intraocular hemorrhage, although uncommon, is a “potentially visually threatening adverse event that has been well documented in patients taking warfarin and other antithrombotics.” A previous meta-analysis found no significant difference in the risk of intraocular bleeding between NOACs and other antithrombotic agents, such as warfarin. However, the authors note that the previous study lacked statistical power. The current meta-analysis was designed to update the earlier one and provide more rigorous and powered data and further elucidate the intraocular risk of treatment with NOACs.

The researchers state that their findings “have particular implications for patients at higher risk of spontaneous retinal and subretinal bleeding” and “may also have important implications in the perioperative period, in which the use of novel oral anticoagulants may be superior.”

They add that “future studies are required to better characterize the optimal management of patients with both ophthalmic disease and cardiovascular comorbidities requiring therapy with anticoagulants.”


Sun MT, Wood MK, Chan W, et al. Risk of Intraocular Bleeding With Novel Oral Anticoagulants Compared With Warfarin: A Systematic Review and Meta-analysis. JAMA Ophthalmol. 2017 Jul 6. [Epub ahead of print]